This study is attempting to clarify the cause of tumor-associated fever in Hodgkin's disease and related lymphomas. By means of cationic electrophoresis in urea-containing polyacrylamide gels, urine, plasma and tissue samples of febrile patients have been assayed for proteins similar in size and charge to the pyrogenic protein "endogenous pyrogen or EP" produced by non-neoplastic inflammatory cells. Plasma from febrile Hodgkin's patients is found to contain trace proteins absent in afebrile individuals; a positive correlation exists between severity of pyrexia and quantity of these proteins. They disappear when effective therapy produces clinical remission. They are also seen in association with other tumor-related fevers, some pyogenic infections and in patients febrile following intratumoral injection of BCG. The urine of febrile Hodgkin's disease patients contains a protein that appears identical in size and charge to one of the trace plasma proteins. This protein has a pI 9, a MW 20,000 and, in some isolates, proteiolytic activity. It hydrolyzes p-nitrophenyl acetate and on storage undergoes transformation to a somewhat large molecule that is identical to the most cathodal acetylesterases found in tissue homogenates. On histochemical sections these esterase isoenzymes have a lysosomal localization. Isolation and comparison of the described proteins is in progress. When practicable they will be compared with respect to size, charge, antigenic determinants, enzymatic activity and pyrogenicity in rabbits.